The goal of this Training Program in HIV Cure (TPHC) is to provide outstanding training in basic, translational, and clinical research toward the HIV Cure agenda to outstanding predoctoral students and highly qualified MD or PhD postdoctoral fellows. The program includes 14 trainers and 8 junior trainers from 8 PhD programs, 11 departments in the School of Medicine, the Lerner College of Medicine, School of Dental Medicine, and the College of Arts and Sciences at Case Western Reserve University, and 9 clinical units at both University Hospitals (UH) Case Medical Center, the Louis Stokes Cleveland VA Medical Center, and the Cleveland Clinic Foundation, and is closely allied with the Case/UH Center for AIDS Research (CFAR). The participating 14 senior faculty is known for excellence in research, ample NIH and foundation funding, and robust research space, and have been specifically selected from a very large complement of excellent CFAR members to provide focus toward the single goal of curing an HIV infection in the periphery, the mucosa, and the brain. To expand the diversity of our trainers and to look to the future, we have also recruited 8 junior faculty, with strong developing programs who have not yet trained many investigators, yet will develop into outstanding preceptors through our co-mentoring program. Training focuses on relating the basic approaches of molecular and cellular virology, genomics, proteomics and systems biology, immunology, and clinical dissection of non-AIDS complications to mechanistic questions and solutions that address viral reservoirs, persistence, latency, immune exhaustion, systemic inflammation, and immune control, with particular emphasis on (a) Viral transcriptional regulation, (b) Host restriction factors, (c) Viral replication and reservoirs, (d) Systemic and mucosal immunity, (e) Clinical trials, (f) Signal transduction and gene expression, and (g) Systems biology and bioinformatics. Predoctoral training is accomplished through enrollment of students who have matriculated in the 8 PhD programs in Molecular Virology, Cell Biology, Immunology, Systems Biology and Bioinformatics, Chemistry, Doctorate of Nursing Practice, Molecular Medicine, and Epidemiology and Biostatistics. The basic coursework and guided training in research skills provided by these departmental programs in the three schools on the Health Sciences Campus, at the Lerner College of Medicine in the Cleveland Clinic Foundation, and in the College of Arts and Sciences, is supplemented and enhanced by TPHC-specific components. Postdoctoral trainees, who are appointed via their recruitment to a TPHC trainer?s lab as well as the CFAR, will also participate in the following programmatic and career development activities: (i) Completion of an additional, required graduate course in the Clinical Research Scholars Program (CRSP) at CWRU [http://casemed.case.edu/crsp] (ii) Participation in an exciting Clinical Immersion Experience in HIV clinical care at the University Hospitals Special Immunology Unit, the Louis Stokes Cleveland VA Medical Center, or the HIV Section of the Department of Infectious Diseases at the Cleveland Clinic Foundation (iii) Representation of the University on the Cleveland HIV Community Action Board (iv) International travel to Kampala, Uganda to interact with patients, scientists, and clinicians at the Joint Clinical Research Center [http://www.jcrc.org.ug], a Center of of Excellence that was started by H.E. President Yoweri Museveni in 1990 to address the very serious problem of HIV/AIDS in Africa (v) Establishing a CFAR-sponsored research working team with other TPHC trainees and the Fogarty trainees from Uganda on the CWRU campus (vi) Guest oral presentations at the CFAR internal and external annual retreats, in addition to the weekly seminar series and monthly journal club, organized by the CFAR, the Center for Global Health, the Division of Infectious Diseases, the Department of Molecular Biology and Microbiology, the Immunology Training Program, and the Molecular Medicine Program at the CCF (vii) Mentoring by a TPHC faculty committee that includes senior trainers and junior trainer faculty who are developing independent programs in cutting-edge areas of HIV Cure research This application seeks 4 positions (2 predocs and 2 mid-career PhD or MD postdocs per year).